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Stem Cells International
Volume 2016 (2016), Article ID 2171035, 16 pages
http://dx.doi.org/10.1155/2016/2171035
Review Article

Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration

Laboratório de Cardiologia Molecular e Celular (LCMC), Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil

Received 14 August 2015; Revised 26 October 2015; Accepted 10 November 2015

Academic Editor: Stefania Montagnani

Copyright © 2016 Maximiliano I. Schaun et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Mozaffarian, E. J. Benjamin, A. S. Go et al., “Heart disease and stroke statistics—2015 update: a report from the American Heart Association,” Circulation, vol. 131, no. 4, pp. e29–e322, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. D. M. Lloyd-Jones, Y. Hong, D. Labarthe et al., “Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond,” Circulation, vol. 121, no. 4, pp. 586–613, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. M. A. Pfeffer and E. Braunwald, “Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications,” Circulation, vol. 81, no. 4, pp. 1161–1172, 1990. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Chen, E. E. Tredget, P. Y. G. Wu, Y. Wu, and Y. Wu, “Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing,” PLoS ONE, vol. 3, no. 4, Article ID e1886, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau, “Paracrine mechanisms in adult stem cell signaling and therapy,” Circulation Research, vol. 103, no. 11, pp. 1204–1219, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. J. S. Burchfield and S. Dimmeler, “Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis,” Fibrogenesis and Tissue Repair, vol. 1, no. 1, article 4, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Abdel-Latif, R. Bolli, I. M. Tleyjeh et al., “Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis,” Archives of Internal Medicine, vol. 167, no. 10, pp. 989–997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. S.-L. Chen, W.-W. Fang, F. Ye et al., “Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction,” The American Journal of Cardiology, vol. 94, no. 1, pp. 92–95, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. E. C. Perin, R. Sanz-Ruiz, P. L. Sánchez et al., “Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: the PRECISE Trial,” American Heart Journal, vol. 168, no. 1, pp. 88.e2–95.e2, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. C. E. Murry, L. J. Field, and P. Menasché, “Cell-based cardiac repair reflections at the 10-year point,” Circulation, vol. 112, no. 20, pp. 3174–3183, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. J. C. Garbern and R. T. Lee, “Cardiac stem cell therapy and the promise of heart regeneration,” Cell Stem Cell, vol. 12, no. 6, pp. 689–698, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Menasché, O. Alfieri, S. Janssens et al., “The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation,” Circulation, vol. 117, no. 9, pp. 1189–1200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. D. T. Vu and T. Kofidis, “Myocardial restoration: is it the cell or the architecture or both?” Cardiology Research and Practice, vol. 2012, Article ID 240497, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Russo, S. Young, A. Hamilton, B. G. Amsden, and L. E. Flynn, “Mesenchymal stem cell delivery strategies to promote cardiac regeneration following ischemic injury,” Biomaterials, vol. 35, no. 13, pp. 3956–3974, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Gonzales and T. Pedrazzini, “Progenitor cell therapy for heart disease,” Experimental Cell Research, vol. 315, no. 18, pp. 3077–3085, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Wang, X. Zhao, C. Kuang et al., “Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway,” PLoS ONE, vol. 7, no. 9, Article ID e43922, 2012. View at Publisher · View at Google Scholar
  17. K. C. Wollert, G. P. Meyer, J. Lotz et al., “Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial,” The Lancet, vol. 364, no. 9429, pp. 141–148, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Bartunek, M. Vanderheyden, B. Vandekerckhove et al., “Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety,” Circulation, vol. 112, no. 9, supplement, pp. I178–I183, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Gyöngyösi, I. Lang, M. Dettke et al., “Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study,” Nature Clinical Practice Cardiovascular Medicine, vol. 6, no. 1, pp. 70–81, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Janssens, C. Dubois, J. Bogaert et al., “Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial,” The Lancet, vol. 367, no. 9505, pp. 113–121, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. V. Jeevanantham, M. Butler, A. Saad, A. Abdel-Latif, E. K. Zuba-Surma, and B. Dawn, “Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis,” Circulation, vol. 126, no. 5, pp. 551–568, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. J. M. Hare, J. E. Fishman, G. Gerstenblith et al., “Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial,” The Journal of the American Medical Association, vol. 308, no. 22, pp. 2369–2379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Bartunek, A. Behfar, D. Dolatabadi et al., “Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics,” Journal of the American College of Cardiology, vol. 61, no. 23, pp. 2329–2338, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Pätilä, M. Lehtinen, A. Vento et al., “Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: a prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass,” Journal of Heart and Lung Transplantation, vol. 33, no. 6, pp. 567–574, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. Y.-J. Yang, H.-Y. Qian, J. Huang et al., “Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts,” European Heart Journal, vol. 29, no. 12, pp. 1578–1590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. Y.-J. Yang, H.-Y. Qian, J. Huang et al., “Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells increases benefits in infarcted swine hearts,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 12, pp. 2076–2082, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Cai, D. Zheng, Y. Dong et al., “Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction,” Acta Biochimica et Biophysica Sinica, vol. 43, no. 11, pp. 857–866, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Vasa, S. Fichtlscherer, K. Adler et al., “Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease,” Circulation, vol. 103, no. 24, pp. 2885–2890, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Qiu, A. Cai, Y. Dong et al., “SDF-1alpha upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects,” Journal of Biomedical Science, vol. 19, article 99, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Wang, X. Chen, W. Zhu, H. Zhang, S. Hu, and X. Cong, “Growth inhibition of mesenchymal stem cells by aspirin: involvement of the wnt/β-catenin signal pathway,” Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 8, pp. 696–701, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Deng, S. Hu, A. R. Baydoun, J. Chen, X. Chen, and X. Cong, “Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β-catenin pathway,” Cell Proliferation, vol. 42, no. 6, pp. 721–730, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Lou, T. J. Povsic, J. D. Allen et al., “The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties,” Thrombosis Research, vol. 126, no. 3, pp. e175–e179, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. F. Hassan, S. Meduru, K. Taguchi et al., “Carvedilol enhances mesenchymal stem cell therapy for myocardial infarction via inhibition of caspase-3 expression,” Journal of Pharmacology and Experimental Therapeutics, vol. 343, no. 1, pp. 62–71, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Numasawa, T. Kimura, S. Miyoshi et al., “Treatment of human mesenchymal stem cells with angiotensin receptor blocker improved efficiency of cardiomyogenic transdifferentiation and improved cardiac function via angiogenesis,” STEM CELLS, vol. 29, no. 9, pp. 1405–1414, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. D. Shinmura, I. Togashi, S. Miyoshi et al., “Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function,” STEM CELLS, vol. 29, no. 2, pp. 357–366, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Ito and T. Suda, “Metabolic requirements for the maintenance of self-renewing stem cells,” Nature Reviews Molecular Cell Biology, vol. 15, no. 4, pp. 243–256, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. The top 10 causes of death [database on the Internet], WHO, http://www.who.int/mediacentre/factsheets/fs310/en/.
  38. E. Antman, J.-P. Bassand, W. Klein et al., “Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: the Joint European Society of Cardiology/American College of Cardiology Committee,” Journal of the American College of Cardiology, vol. 36, no. 3, pp. 959–969, 2000. View at Publisher · View at Google Scholar
  39. E. Boersma, N. Mercado, D. Poldermans, M. Gardien, J. Vos, and M. L. Simoons, “Acute myocardial infarction,” The Lancet, vol. 361, no. 9360, pp. 847–858, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. D. L. Mann, “Mechanisms and models in heart failure: a combinatorial approach,” Circulation, vol. 100, no. 9, pp. 999–1008, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. K. Ono, A. Matsumori, T. Shioi, Y. Furukawa, and S. Sasayama, “Cytokine gene expression after myocardial lnfarction in rat hearts: possible implication in left ventricular remodeling,” Circulation, vol. 98, no. 2, pp. 149–156, 1998. View at Publisher · View at Google Scholar · View at Scopus
  42. S. W. Werns and B. R. Lucchesi, “Inflammation and myocardial infarction,” British Medical Bulletin, vol. 43, no. 2, pp. 460–471, 1987. View at Google Scholar · View at Scopus
  43. S. Kinugawa, H. Tsutsui, S. Hayashidani et al., “Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress,” Circulation Research, vol. 87, no. 5, pp. 392–398, 2000. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Ide, H. Tsutsui, S. Kinugawa et al., “Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium,” Circulation Research, vol. 86, no. 2, pp. 152–157, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. B. E. Strauer, M. Brehm, T. Zeus et al., “Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans,” Circulation, vol. 106, no. 15, pp. 1913–1918, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. V. Schächinger, A. Aicher, N. Döbert et al., “Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium,” Circulation, vol. 118, no. 14, pp. 1425–1432, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Tavassoli and C. L. Hardy, “Molecular basis of homing of intravenously transplanted stem cells to the marrow,” Blood, vol. 76, no. 6, pp. 1059–1070, 1990. View at Google Scholar · View at Scopus
  48. M. Shi, J. Li, L. Liao et al., “Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice,” Haematologica, vol. 92, no. 7, pp. 897–904, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Kronenwett, S. Martin, and R. Haas, “The role of cytokines and adhesion molecules for mobilization of peripheral blood stem cells,” STEM CELLS, vol. 18, no. 5, pp. 320–330, 2000. View at Publisher · View at Google Scholar · View at Scopus
  50. X. Hu, S. Dai, W.-J. Wu et al., “Stromal cell-derived factor-1α confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell-derived factor-1α-CXCR4 axis,” Circulation, vol. 116, no. 6, pp. 654–663, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. D. J. Hausenloy and D. M. Yellon, “Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection,” Heart Failure Reviews, vol. 12, no. 3-4, pp. 217–234, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. B. Vrtovec, G. Poglajen, and F. Haddad, “Stem cell therapy in patients with heart failure,” Methodist DeBakey Cardiovascular Journal, vol. 9, no. 1, pp. 6–10, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Hou, K.-M. Yang, H. Zhang et al., “Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats,” International Journal of Cardiology, vol. 115, no. 2, pp. 220–228, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Mazo, V. Planat-Bénard, G. Abizanda et al., “Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction,” European Journal of Heart Failure, vol. 10, no. 5, pp. 454–462, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Orlic, J. Kajstura, S. Chimenti, D. M. Bodine, A. Leri, and P. Anversa, “Bone marrow stem cells regenerate infarcted myocardium,” Pediatric Transplantation, vol. 7, supplement3, pp. 86–88, 2003. View at Google Scholar
  56. I. Francischetti, J. B. Moreno, M. Scholz, and W. B. Yoshida, “Leukocytes and the inflammatory response in ischemia-reperfusion injury,” Brazilian Journal of Cardiovascular Surgery, vol. 25, no. 4, pp. 575–584, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Elsässer, M. Schlepper, W.-P. Klövekorn et al., “Hibernating myocardium: an incomplete adaptation to ischemia,” Circulation, vol. 96, no. 9, pp. 2920–2931, 1997. View at Publisher · View at Google Scholar · View at Scopus
  58. N. G. Frangogiannis, S. Shimoni, S. M. Chang et al., “Evidence for an active inflammatory process in the hibernating human myocardium,” The American Journal of Pathology, vol. 160, no. 4, pp. 1425–1433, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. M. J. Lipinski, G. G. Biondi-Zoccai, A. Abbate et al., “Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials,” Journal of the American College of Cardiology, vol. 50, no. 18, pp. 1761–1767, 2007. View at Google Scholar
  60. K. A. Gerbin and C. E. Murry, “The winding road to regenerating the human heart,” Cardiovascular Pathology, vol. 24, no. 3, pp. 133–140, 2015. View at Google Scholar
  61. B. Assmus, S. Dimmeler, and A. M. Zeiher, “Cardiac cell therapy: lost in meta-analyses,” Circulation Research, vol. 116, no. 8, pp. 1291–1292, 2015. View at Google Scholar
  62. T. J. Nelson, A. Martinez-Fernandez, S. Yamada, C. Perez-Terzic, Y. Ikeda, and A. Terzic, “Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells,” Circulation, vol. 120, no. 5, pp. 408–416, 2009. View at Publisher · View at Google Scholar
  63. A. Kawamoto, T. Tkebuchava, J.-I. Yamaguchi et al., “Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia,” Circulation, vol. 107, no. 3, pp. 461–468, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. M. S. Penn, J. Pastore, T. Miller, and R. Aras, “SDF-1 in myocardial repair,” Gene Therapy, vol. 19, no. 6, pp. 583–587, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Eibel, C. G. Rodrigues, I. I. Giusti et al., “Gene therapy for ischemic heart disease: review of clinical trials,” Brazilian Journal of Cardiovascular Surgery, vol. 26, no. 4, pp. 635–646, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. M. Lavu, S. Gundewar, and D. J. Lefer, “Gene therapy for ischemic heart disease,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 5, pp. 742–750, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Asahara, C. Kalka, and J. M. Isner, “Stem cell therapy and gene transfer for regeneration,” Gene Therapy, vol. 7, no. 6, pp. 451–457, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Rehman, J. Li, C. M. Orschell, and K. L. March, “Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors,” Circulation, vol. 107, no. 8, pp. 1164–1169, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. C. Urbich, A. Aicher, C. Heeschen et al., “Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells,” Journal of Molecular and Cellular Cardiology, vol. 39, no. 5, pp. 733–742, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Gnecchi, H. He, O. D. Liang et al., “Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells,” Nature Medicine, vol. 11, no. 4, pp. 367–368, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. B.-E. Strauer and G. Steinhoff, “10 Years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice,” Journal of the American College of Cardiology, vol. 58, no. 11, pp. 1095–1104, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. R. T. Sant'anna, R. A. K. Kalil, A. S. Pretto Neto et al., “Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action,” Cell Transplantation, vol. 19, no. 8, pp. 959–964, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. V. Schächinger, B. Assmus, S. Erbs et al., “Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial,” European Journal of Heart Failure, vol. 11, no. 10, pp. 973–979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. V. J. Dzau, M. Gnecchi, and A. S. Pachori, “Enhancing stem cell therapy through genetic modification,” Journal of the American College of Cardiology, vol. 46, no. 7, pp. 1351–1353, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. H. K. Haider, S. Jiang, N. M. Idris, and M. Ashraf, “IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair,” Circulation Research, vol. 103, no. 11, pp. 1300–1308, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. R. Sanz-Ruiz, E. Gutiérrez Ibañes, A. V. Arranz, M. E. Fernández Santos, P. L. Fernández, and F. Fernández-Avilés, “Phases I–III clinical trials using adult stem cells,” Stem Cells International, vol. 2010, Article ID 579142, 12 pages, 2010. View at Publisher · View at Google Scholar
  77. J. J. H. Chong, X. Yang, C. W. Don et al., “Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts,” Nature, vol. 510, no. 7504, pp. 273–277, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. T.-S. Li, K. Cheng, K. Malliaras et al., “Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells,” Journal of the American College of Cardiology, vol. 59, no. 10, pp. 942–953, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. R. J. Hassink, A. B. de la Rivière, C. L. Mummery, and P. A. Doevendans, “Transplantation of cells for cardiac repair,” Journal of the American College of Cardiology, vol. 41, no. 5, pp. 711–717, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. K. Thygesen, J. S. Alpert, and H. D. White, “Universal definition of myocardial infarction,” European Heart Journal, vol. 28, no. 20, pp. 2525–2538, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Song, Y.-J. Yang, Q.-T. Dong et al., “Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase,” PLoS ONE, vol. 8, no. 5, Article ID e65702, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. T. E. Robey, M. K. Saiget, H. Reinecke, and C. E. Murry, “Systems approaches to preventing transplanted cell death in cardiac repair,” Journal of Molecular and Cellular Cardiology, vol. 45, no. 4, pp. 567–581, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Ebrahim, F. C. Taylor, and P. Brindle, “Statins for the primary prevention of cardiovascular disease,” British Medical Journal, vol. 348, article g280, 2014. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Bauersachs, P. Galuppo, D. Fraccarollo, M. Christ, and G. Ertl, “Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme A reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction,” Circulation, vol. 104, no. 9, pp. 982–985, 2001. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Hayashidani, H. Tsutsui, T. Shiomi et al., “Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction,” Circulation, vol. 105, no. 7, pp. 868–873, 2002. View at Publisher · View at Google Scholar · View at Scopus
  86. A. Blum and R. Shamburek, “The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis,” Atherosclerosis, vol. 203, no. 2, pp. 325–330, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. Q. Dong, Y. Yang, L. Song, H. Qian, and Z. Xu, “Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating AMP-activated protein kinase,” International Journal of Cardiology, vol. 153, no. 3, pp. 311–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. E. H. Awtry and J. Loscalzo, “Aspirin,” Circulation, vol. 101, no. 10, pp. 1206–1218, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. E. Castaño, M. Dalmau, M. Martí, F. Berrocal, R. Bartrons, and J. Gil, “Inhibition of DNA synthesis by aspirin in Swiss 3T3 fibroblasts,” The Journal of Pharmacology and Experimental Therapeutics, vol. 280, no. 1, pp. 366–372, 1997. View at Google Scholar
  90. L. Ling, V. Nurcombe, and S. M. Cool, “Wnt signaling controls the fate of mesenchymal stem cells,” Gene, vol. 433, no. 1-2, pp. 1–7, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. P. Larochelle, S. W. Tobe, and Y. Lacourcière, “β-Blockers in hypertension: studies and meta-analyses over the years,” Canadian Journal of Cardiology, vol. 30, no. 5, supplement, pp. S16–S22, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. S. L. Kopecky, “Effect of beta blockers, particularly carvedilol, on reducing the risk of events after acute myocardial infarction,” The American Journal of Cardiology, vol. 98, no. 8, pp. 1115–1119, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Cargnoni, C. Ceconi, P. Bernocchi et al., “Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic myocardium viability,” Cardiovascular Research, vol. 47, no. 3, pp. 556–566, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. J. Stiles, C. Amaya, R. Pham et al., “Propranolol treatment of infantile hemangioma endothelial cells: a molecular analysis,” Experimental and Therapeutic Medicine, vol. 4, no. 4, pp. 594–604, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. F. Sharifpanah, F. Saliu, M. M. Bekhite, M. Wartenberg, and H. Sauer, “β-adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signalling,” Cell and Tissue Research, vol. 358, no. 2, pp. 443–452, 2014. View at Publisher · View at Google Scholar · View at Scopus
  96. E. Viola, A. Coggiola Pittoni, A. Drahos, U. Moretti, and A. Conforti, “Photosensitivity with angiotensin II receptor blockers: a retrospective study using data from VigiBase,” Drug Safety, vol. 38, no. 10, pp. 889–894, 2015. View at Publisher · View at Google Scholar
  97. C. C. Cesa, S. M. Barbiero, O. Petkowicz Rde et al., “Effectiveness of physical exercise to reduce cardiovascular risk factors in youths: a randomized clinical trial,” Journal of Clinical Medicine Research, vol. 7, no. 5, pp. 348–355, 2015. View at Publisher · View at Google Scholar
  98. B. S. Heran, J. M. Chen, S. Ebrahim et al., “Exercise-based cardiac rehabilitation for coronary heart disease,” Cochrane Database of Systematic Reviews, vol. 7, Article ID CD001800, 2011. View at Google Scholar · View at Scopus
  99. F. W. Booth, C. K. Roberts, and M. J. Laye, “Lack of exercise is a major cause of chronic diseases,” Comprehensive Physiology, vol. 2, no. 2, pp. 1143–1211, 2012. View at Publisher · View at Google Scholar · View at Scopus
  100. S. Sciarretta, P. Zhai, D. Shao et al., “Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome,” Circulation, vol. 125, no. 9, pp. 1134–1146, 2012. View at Publisher · View at Google Scholar · View at Scopus
  101. B. V. Howard, L. Van Horn, J. Hsia et al., “Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial,” The Journal of the American Medical Association, vol. 295, no. 6, pp. 655–666, 2006. View at Publisher · View at Google Scholar
  102. M. de Lorgeril and P. Salen, “The Mediterranean-style diet for the prevention of cardiovascular diseases,” Public Health Nutrition, vol. 9, no. 1, pp. 118–123, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. The Diabetes Prevention Program, “Design and methods for a clinical trial in the prevention of type 2 diabetes,” Diabetes Care, vol. 22, no. 4, pp. 623–634, 1999. View at Publisher · View at Google Scholar
  104. J. Lindström, A. Louheranta, M. Mannelin et al., “The Finnish Diabetes Prevention Study (DPS): lifestyle intervention and 3-year results on diet and physical activity,” Diabetes Care, vol. 26, no. 12, pp. 3230–3236, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Keys, “Mediterranean diet and public health: personal reflections,” The American Journal of Clinical Nutrition, vol. 61, no. 6, supplement, pp. 1321S–1323S, 1995. View at Google Scholar · View at Scopus
  106. M. de Lorgeril, S. Renaud, N. Mamelle et al., “Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease,” The Lancet, vol. 343, no. 8911, pp. 1454–1459, 1994. View at Publisher · View at Google Scholar · View at Scopus
  107. H. Gardener, C. B. Wright, Y. Gu et al., “Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study,” American Journal of Clinical Nutrition, vol. 94, no. 6, pp. 1458–1464, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. M. C. D. Thomazella, M. F. S. Góes, C. R. Andrade et al., “Effects of high adherence to mediterranean or low-fat diets in medicated secondary prevention patients,” The American Journal of Cardiology, vol. 108, no. 11, pp. 1523–1529, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. H. M. Blau, T. R. Brazelton, and J. M. Weimann, “The evolving concept of a stem cell: entity or function?” Cell, vol. 105, no. 7, pp. 829–841, 2001. View at Publisher · View at Google Scholar · View at Scopus
  110. W. L. Fodor, “Tissue engineering and cell based therapies, from the bench to the clinic: the potential to replace, repair and regenerate,” Reproductive Biology and Endocrinology, vol. 1, article 102, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. N. Gorbunov, G. Petrovski, N. Gurusamy, D. Ray, D. H. Kim, and D. K. Das, “Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells,” Journal of Cellular and Molecular Medicine, vol. 16, no. 1, pp. 174–184, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. U. N. Das, “Essential fatty acids—a review,” Current Pharmaceutical Biotechnology, vol. 7, no. 6, pp. 467–482, 2006. View at Google Scholar
  113. B. M. Shewchuk, “Prostaglandins and n-3 polyunsaturated fatty acids in the regulation of the hypothalamic-pituitary axis,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 91, no. 6, pp. 277–287, 2014. View at Publisher · View at Google Scholar · View at Scopus
  114. S. V. Martins, A. Madeira, P. A. Lopes et al., “Adipocyte membrane glycerol permeability is involved in the anti-adipogenic effect of conjugated linoleic acid,” Biochemical and Biophysical Research Communications, vol. 458, no. 2, pp. 356–361, 2015. View at Publisher · View at Google Scholar · View at Scopus
  115. D. L. A. Greenway and K. G. H. Dyke, “Mechanism of the inhibitory action of linoleic acid on the growth of Staphylococcus aureus,” Journal of General Microbiology, vol. 115, no. 1, pp. 233–245, 1979. View at Publisher · View at Google Scholar · View at Scopus
  116. J. Tumova, M. Andel, and J. Trnka, “Excess of free fatty acids as a cause of metabolic dysfunction in skeletal muscle,” Physiological Research, In press.
  117. Y. Kawamori, Y. Katayama, N. Asada et al., “Role for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche,” Blood, vol. 116, no. 25, pp. 5528–5535, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. M. S. K. Wong, M. S. Leisegang, C. Kruse et al., “Vitamin D promotes vascular regeneration,” Circulation, vol. 130, no. 12, pp. 976–986, 2014. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. Higashi and M. Yoshizumi, “Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients,” Pharmacology and Therapeutics, vol. 102, no. 1, pp. 87–96, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. F. W. Booth and D. B. Thomason, “Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models,” Physiological Reviews, vol. 71, no. 2, pp. 541–585, 1991. View at Google Scholar · View at Scopus
  121. J. Henriksson, M. M.-Y. Chi, C. S. Hintz et al., “Chronic stimulation of mammalian muscle: changes in enzymes of six metabolic pathways,” The American Journal of Physiology—Cell Physiology, vol. 251, no. 4, part 1, pp. C614–C632, 1986. View at Google Scholar · View at Scopus
  122. R. S. Williams, “Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event,” The Journal of Biological Chemistry, vol. 261, no. 26, pp. 12390–12394, 1986. View at Google Scholar · View at Scopus
  123. J. R. Minotti, E. C. Johnson, T. L. Hudson et al., “Skeletal muscle response to exercise training in congestive heart failure,” Journal of Clinical Investigation, vol. 86, no. 3, pp. 751–758, 1990. View at Publisher · View at Google Scholar · View at Scopus
  124. A. J. S. Coats, S. Adamopoulos, A. Radaelli et al., “Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function,” Circulation, vol. 85, no. 6, pp. 2119–2131, 1992. View at Publisher · View at Google Scholar · View at Scopus
  125. C. A. Emter, S. A. McCune, G. C. Sparagna, M. J. Radin, and R. L. Moore, “Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 289, no. 5, pp. H2030–H2038, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. C. A. DeSouza, L. F. Shapiro, C. M. Clevenger et al., “Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men,” Circulation, vol. 102, no. 12, pp. 1351–1357, 2000. View at Publisher · View at Google Scholar · View at Scopus
  127. M. G. Gunning, J. Walker, S. Eastick, J. B. Bomanji, P. J. Ell, and J. M. Walker, “Exercise training following myocardial infarction improves myocardial perfusion assessed by thallium-201 scintigraphy,” International Journal of Cardiology, vol. 84, no. 2-3, pp. 233–239, 2002. View at Publisher · View at Google Scholar · View at Scopus
  128. J. C. Quindry, K. L. Hamilton, J. P. French et al., “Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis,” Journal of Applied Physiology, vol. 103, no. 3, pp. 1056–1062, 2007. View at Publisher · View at Google Scholar · View at Scopus
  129. R. B. Nunes, J. P. Alves, L. P. Kessler, and P. dal Lago, “Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats,” Clinics, vol. 68, no. 6, pp. 876–882, 2013. View at Publisher · View at Google Scholar · View at Scopus
  130. R. M. Melo, E. Martinho Jr., and L. C. Michelini, “Training-induced, pressure-lowering effect in SHR: wide effects on circulatory profile of exercised and nonexercised muscles,” Hypertension, vol. 42, no. 4, pp. 851–857, 2003. View at Publisher · View at Google Scholar · View at Scopus
  131. U. Laufs, N. Werner, A. Link et al., “Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis,” Circulation, vol. 109, no. 2, pp. 220–226, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. E. Eleuteri, A. Mezzani, A. Di Stefano et al., “Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report,” Biomarkers, vol. 18, no. 5, pp. 418–424, 2013. View at Publisher · View at Google Scholar · View at Scopus
  133. M. I. Schaun, T. Dipp, J. Da Silva Rossato et al., “The effects of periodized concurrent and aerobic training on oxidative stress parameters, endothelial function and immune response in sedentary male individuals of middle age,” Cell Biochemistry and Function, vol. 29, no. 7, pp. 534–542, 2011. View at Publisher · View at Google Scholar · View at Scopus
  134. R. G. Turan, M. Brehm, M. Köstering et al., “Effects of exercise training on mobilization of BM-CPCs and migratory capacity as well as LVEF after AMI,” Medizinische Klinik, vol. 101, supplement 1, pp. 198–201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  135. P. Sarto, E. Balducci, G. Balconi et al., “Effects of exercise training on endothelial progenitor cells in patients with chronic heart failure,” Journal of Cardiac Failure, vol. 13, no. 9, pp. 701–708, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. W.-H. Xia, J. Li, C. Su et al., “Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men,” Aging Cell, vol. 11, no. 1, pp. 111–119, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. S. Adamopoulos, J. Parissis, C. Kroupis et al., “Physical training reduces peripheral markers of inflammation in patients with chronic heart failure,” European Heart Journal, vol. 22, no. 9, pp. 791–797, 2001. View at Publisher · View at Google Scholar · View at Scopus
  138. D. J. Ceradini, A. R. Kulkarni, M. J. Callaghan et al., “Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1,” Nature Medicine, vol. 10, no. 8, pp. 858–864, 2004. View at Publisher · View at Google Scholar · View at Scopus
  139. B. Rinaldi, M. Donniacuo, L. Sodano et al., “Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training,” PLoS ONE, vol. 8, no. 7, Article ID e69954, 2013. View at Publisher · View at Google Scholar · View at Scopus
  140. C. A. Pinho, C. B. Tromm, A. M. V. Tavares et al., “Effects of different physical training protocols on ventricular oxidative stress parameters in infarction-induced rats,” Life Sciences, vol. 90, no. 13-14, pp. 553–559, 2012. View at Publisher · View at Google Scholar · View at Scopus
  141. B. Halliwell, “Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans,” Free Radical Research, vol. 25, no. 1, pp. 57–74, 1996. View at Publisher · View at Google Scholar · View at Scopus
  142. A. Ghorbani and H. Naderi-Meshkin, “The endocrine regulation of stem cells: physiological importance and pharmacological potentials for cell-based therapy,” Current Stem Cell Research & Therapy, vol. 10, p. 1, 2015. View at Publisher · View at Google Scholar
  143. V. Karantalis and J. M. Hare, “Use of mesenchymal stem cells for therapy of cardiac disease,” Circulation Research, vol. 116, no. 8, pp. 1413–1430, 2015. View at Publisher · View at Google Scholar
  144. J. Liu, K. H. Narsinh, F. Lan et al., “Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging,” Circulation: Cardiovascular Imaging, vol. 5, no. 4, pp. 481–490, 2012. View at Publisher · View at Google Scholar · View at Scopus
  145. S. A. Fisher, C. Doree, A. Mathur, and E. Martin-Rendon, “Meta-analysis of cell therapy trials for patients with heart failure,” Circulation Research, vol. 116, no. 8, pp. 1361–1377, 2015. View at Google Scholar
  146. M. Gyöngyösi, W. Wojakowski, P. Lemarchand et al., “Meta-analysis of cell-based cardiac studies (ACCRUE) in patients with acute myocardial infarction based on individual patient data,” Circulation Research, vol. 116, no. 8, pp. 1346–1360, 2015. View at Publisher · View at Google Scholar
  147. I. I. Giusti, C. G. Rodrigues, F. B. Salles et al., “High doses of vascular endothelial growth factor 165 safely, but transiently, improve myocardial perfusion in no-option ischemic disease,” Human Gene Therapy Methods, vol. 24, no. 5, pp. 298–306, 2013. View at Publisher · View at Google Scholar · View at Scopus
  148. S.-G. Ong, W. H. Lee, M. Huang et al., “Cross talk of combined gene and cell therapy in ischemic heart disease: role of exosomal microRNA transfer,” Circulation, vol. 130, supplement 1, no. 11, pp. S60–S69, 2014. View at Publisher · View at Google Scholar · View at Scopus
  149. R. C. Lai, F. Arslan, M. M. Lee et al., “Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury,” Stem Cell Research, vol. 4, no. 3, pp. 214–222, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. K. Iekushi, F. Seeger, B. Assmus, A. M. Zeiher, and S. Dimmeler, “Regulation of cardiac microRNAs by bone marrow mononuclear cell therapy in myocardial infarction,” Circulation, vol. 125, no. 14, pp. 1765–1773, 2012. View at Publisher · View at Google Scholar · View at Scopus
  151. A. Caporali and C. Emanueli, “MicroRNAs in postischemic vascular repair,” Cardiology Research and Practice, vol. 2012, Article ID 486702, 7 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  152. H. Masumoto, T. Matsuo, K. Yamamizu et al., “Pluripotent stem cell-engineered cell sheets reassembled with defined cardiovascular populations ameliorate reduction in infarct heart function through cardiomyocyte-mediated neovascularization,” STEM CELLS, vol. 30, no. 6, pp. 1196–1205, 2012. View at Publisher · View at Google Scholar · View at Scopus
  153. J. Fujita, Y. Itabashi, T. Seki et al., “Myocardial cell sheet therapy and cardiac function,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 303, no. 10, pp. H1169–H1182, 2012. View at Publisher · View at Google Scholar · View at Scopus
  154. H. Masumoto, T. Ikuno, M. Takeda et al., “Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration,” Scientific Reports, vol. 4, article 6716, 2014. View at Publisher · View at Google Scholar
  155. D. Zhang, W. Huang, B. Dai et al., “Genetically manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 299, no. 5, pp. H1339–H1347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  156. H. Kobayashi, T. Shimizu, M. Yamato et al., “Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts,” Journal of Artificial Organs, vol. 11, no. 3, pp. 141–147, 2008. View at Publisher · View at Google Scholar · View at Scopus
  157. J. V. Terrovitis, R. R. Smith, and E. Marbán, “Assessment and optimization of cell engraftment after transplantation into the heart,” Circulation Research, vol. 106, no. 3, pp. 479–494, 2010. View at Publisher · View at Google Scholar · View at Scopus